International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy

Abstract

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON.

The Evaluation of Optic Nerves Using 7 Tesla “Silent” Zero Echo Time Imaging in Patients with Leber’s Hereditary Optic Neuropathy with or without Idebenone Treatment

“…Idebenone, a short-chain analogue of ubiquinone, has an ability to shuttle electrons from complexes I and II to complex III. Clinical trials proved the visual benefit after Idebenone treatment and suggest that when used within the time window, it may prevent the retinal ganglion cell death [29][30][31][32][46][47][48][49][50][51][52]. Disease onset among LHON carriers is characterized by acute or subacute painless loss of central vision, which is unilateral at the beginning; the other eye is usually affected within six to eight weeks, which may suggest more advanced abnormalities within the single starting nerve [53].…”

Visual function in chronic Leber’s hereditary optic neuropathy during idebenone treatment initiated 5 to 50 years after onset

“…However, its therapeutic effects are still under investigation and a matter of debate. A recently published international consensus statement evaluated the available evidence about the clinical and therapeutic management of LHON and recommended that idebenone should be the standard therapy for genetically confirmed LHON in the first year after disease onset [10]. It was also determined that no evidence exists for treatment of patients with a disease duration of more than 5 years.…”

Strategies for fighting mitochondrial diseases

“…Idebenone is a compound structurally related to CoQ and is the first drug approved by EMA (European Medicines Agency) for the therapy of Leber’s Hereditary Optic Neuropathy (LHON), with an indication for the treatment in patients with acute, subacute or dynamic clinical course, whereas it was not recommended for the treatment for chronic patients [49].…”